Grafted Human iPS Cell-Derived Oligodendrocyte Precursor Cells Contribute to Robust Remyelination of Demyelinated Axons after Spinal Cord Injury

Kawabata, Soya; Takano, Morito; Numasawa-Kuroiwa, Yuko; Itakura, Go; Kobayashi, Yoshiomi; Nishiyama, Yuichiro; Sugai, Keiko; Nishimura, Soraya; Iwai, Hiroki; Isoda, Miho; Shibata, Shinsuke; Kohyama, Jun; Iwanami, Akio; Toyama, Yoshiaki; Matsumoto, Morio; Nakamura, Masaya; Okano, Hideyuki

doi:10.1016/j.stemcr.2015.11.013

Cited by 141 publications

(125 citation statements)

References 29 publications

(39 reference statements)

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“…We also found that after transplantation, rats showed better functional recovery in subgroups transplanted with iPSC induced from female (IMR90) human fetal lung fibroblasts, which may survive at the lesion site. This finding is in accordance with previous findings [38] showing that transplantation of iPSC derived from this source also facilitate axonal regrowth as well as improved functional and electrophysiological recovery.…”

Section: Discussionsupporting

confidence: 93%

Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

Qin

Guo

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Spinal cord injury (SCI) has long been a subject of great interest in a wide range of scientific fields. Several attempts have been made to demonstrate motor function improvement in rats with SCI after transplantation of induced pluripotent stem cells (iPSC). This systematic review and meta-analysis was designed to summarize the effects of iPSC on locomotor recovery in rat models of SCI. Methods: We searched the publications in the PubMed, Medline, Science Citation Index, Cochrane Library, CNKI, and Wan-fang databases and the China Biology Medicine disc. Results were analyzed by Review Manager 5.3.0. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: Six randomized controlled preclinical trials covering eight comparisons and including 212 rats were selected. The subgroup analyses were based on the following items: different SCI models, cell counts, iPSC sources, iPSC differentiations and transplantation methods. The pooled results indicated that iPSC transplantation significantly improved locomotor recovery of rats after SCI by sustaining beneficial effects, especially in the subgroups of contusion, moderate cell counts (5×10⁵), source of human fetal lung fibroblasts, iPSC-neural precursors and intraspinal injection. Conclusion: Our meta-analysis of the effects of iPSC transplantation on locomotor function in SCI models is, to our knowledge, the first meta-analysis in this field. We conclude that iPSC transplantation improves locomotor recovery in rats with SCI, implicating this strategy as an effective therapy. However, more studies are required to validate our conclusions.

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Section: Discussionsupporting

confidence: 93%

Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

Qin

Guo

Yang

et al. 2018

Cell Physiol Biochem

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“…These advances may be the harbingers of more effective approaches towards spinal cord repair, using grafted NSCs or lineage-restricted spinal neuronal progenitors (Roy et al, 2004). Once such local circuit reconstruction is accomplished, then adjunctive approaches such as olfactory ensheathing cell (Granger et al, 2012) and glial progenitor cell delivery (Buchet et al, 2011; Kawabata et al, 2016; Mozafari et al, 2015), respectively designed to generate peripheral and central myelin and hence improve conduction within locally-restored networks, may be productively deployed to potentiate recovery. Indeed, the need for multimodal biological therapies in SCI is highlighted by the additional benefit potentially gained by combining cell transplantation with matrix-modifying enzymes so as to facilitate donor cell integration (Ikegami et al, 2005).…”

Section: Hype: Limits To Therapeutic Advancementioning

confidence: 99%

Stem and Progenitor Cell-Based Therapy of the Central Nervous System: Hopes, Hype, and Wishful Thinking

2016

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A variety of neurological disorders are attractive targets for stem and progenitor cell-based therapy. Yet many conditions are not, whether by virtue of an inhospitable disease environment, poorly understood pathophysiology, or poor alignment of donor cell capabilities with patient needs. Moreover, some disorders may be medically feasible targets, but are not practicable, in light of already available treatments, poor risk-benefit and cost-benefit profiles, or resource limitations. This Perspective seeks to define those neurological conditions most appropriate for cell replacement therapy, by considering its potential efficacy and clinical feasibility in those disorders, as well as potential impediments to its application.

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“…Recently, Kawabata et al . () induced OPCs from hiPSC‐NPCs, previously described by our group (Nori et al . ), and injected them into a NOD/SCID mouse model of SCI.…”

Section: Human Ipsc‐derived Npcsmentioning

confidence: 99%

Applications of induced pluripotent stem cell technologies in spinal cord injury

Nagoshi

Okano

2017

Journal of Neurochemistry

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Numerous basic research studies have suggested the potential efficacy of neural precursor cell (NPC) transplantation in spinal cord injury (SCI). However, in most such studies, the origin of the cells used was mainly fetal tissue or embryonic stem cells, both of which carry potential ethical concerns with respect to clinical use. The development of induced pluripotent stem cells (iPSCs) opened a new path toward regenerative medicine for SCI. iPSCs can be generated from somatic cells by induction of transcription factors, and induced to differentiate into NPCs with characteristics of cells of the central nervous system. The beneficial effect of iPSC-derived NPC transplantation has been reported from our group and others working in rodent and non-human primate models. These promising results facilitate the application of iPSCs for clinical applications in SCI patients. However, iPSCs also have issues, such as genetic/epigenetic abnormalities and tumorigenesis because of the artificial induction method, that must be addressed prior to clinical use. The selection of somatic cells, generation of integration-free iPSCs, and characterization of differentiated NPCs with thorough quality management are all needed to address these potential risks. To enhance the efficacy of the transplanted iPSC-NPCs, especially at chronic phase of SCI, administration of a chondroitinase or semaphorin3A inhibitor represents a potentially important means of promoting axonal regeneration through the lesion site. The combined use of rehabilitation with such cell therapy approaches is also important, as repetitive training enhances neurite outgrowth of transplanted cells and strengthens neural circuits at central pattern generators. Our group has already evaluated clinical grade iPSC-derived NPCs, and we look forward to initiating clinical testing as the next step toward determining whether this approach is safe and effective for clinical use.

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Grafted Human iPS Cell-Derived Oligodendrocyte Precursor Cells Contribute to Robust Remyelination of Demyelinated Axons after Spinal Cord Injury

Cited by 141 publications

References 29 publications

Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

Stem and Progenitor Cell-Based Therapy of the Central Nervous System: Hopes, Hype, and Wishful Thinking

Applications of induced pluripotent stem cell technologies in spinal cord injury

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